Chemical clue sheds light on winter depression

The brains of people with seasonal depression may be too efficient at bundling away a key chemical, a new study suggests.

The finding in people with (SAD) backs the prevailing theory about the biochemical causes of depression, and could give clues into new ways to treat the condition.

The prevailing theory of depression is that affected people do not have enough of certain neurotransmitters called monoamines – serotonin, norepinephrine, and dopamine – in the spaces between neurons. Most modern antidepressants work by blocking the absorption of these neurotransmitters back into the cell.

However, there is little agreement on why levels are inadequate in the first place. It could be that depressed people produce lower volumes of the neurotransmitters, or they could break them down too rapidly. Or it could be that the neurotransmitters are removed from the junction between neurons, called the synaptic cleft, too quickly.

Advertisement

Matthaeus Willeit and Harald Sitte at the University of Vienna in Austria and their colleagues now have evidence for the last of these – that serotonin is being removed too efficiently.

Chemical pump

The researchers studied 73 drug-free patients with seasonal affective disorder (SAD) and 70 people without the condition. People with SAD get depressed in the autumn and winter, and often go into remission in the spring and summer. So-called “bright light therapy” – where sufferers stare at brightly lit screens – can also relieve symptoms.

The researchers were interested in these patients’ serotonin transporter (SERT) – a molecule that “pumps” serotonin back into cells. SERT is expressed in blood platelets, so they drew blood at three points in time&colon; in the autumn or winter (when patients were experiencing seasonal depression), after four weeks of light therapy, and again in summer.

They tested the platelets to see how much SERT was expressed there, and found levels were normal in both groups. They then measured how many times per minute the SERT would go to work removing serotonin, and here they found significant differences.

In blood taken during winter depression, SAD patients had significantly more removal events per minute than those in the healthy control group – about 350 compared with 200.

The process “is too efficient”, says Willeit. After therapy, in people who got better, the number of removal events declined. In those who did not improve, the numbers stayed the same. In summer, SAD patients’ removal events slowed to normal levels.

The finding lends support to the hypothesis that serotonin levels are key to seasonal affective disorder, and specifically suggests that at least part of the problem of depression is that the SERT becomes hyperactive, says Willeit. Exactly how light can modulate its activity is unclear, but worth exploring for possible future therapies, he adds.